Repligen Corporation (NASDAQ:RGEN) today announced positive results from a Phase 1 study to evaluate the pharmacokinetic (PK) and safety profile of RG3039, a novel small molecule drug candidate for the potential treatment of SMA.

PRLog - Apr. 25, 2012 - SMA is a inherited neurodegenerative disease in which symptoms of progressive damage to motor neurons including loss of muscle function typically appear very early in life and often progress to severe physical disability and early loss of life. The Phase 1 trial was a blinded, ascending, single dose study of RG3039 administered to 32 healthy volunteers. The study results demonstrate that RG3039 was well tolerated at all doses administered, with no serious adverse events reported. The data also showed evidence of a dose-related drug response resulting in 90% inhibition of the target enzyme. These outcomes may help to establish appropriate RG3039 dosing regimens for future studies, including potential efficacy studies in SMA patients.

“The safety and PK outcomes from our Phase 1 study of RG3039 are encouraging, and we look forward to initiating the next steps for this drug candidate in alignment with guidance from the U.S. Food and Drug Administration,” said Walter C. Herlihy, President and Chief Executive Officer of Repligen. “The agency has previously granted Orphan Drug and Fast Track designations to RG3039, in recognition of the unmet medical need that exists for patients with SMA and the urgency to advance a treatment for this devastating disease.”

Repligen licensed RG3039 in 2009 from Families of Spinal Muscular Atrophy (FSMA), a patient advocacy organization that funded and directed the preclinical development of RG3039 with an investment of more than $13 million. This was the first drug discovery program ever conducted specifically for SMA. Repligen's research efforts including this Phase 1 study have been partially supported by a grant from the Muscular Dystrophy Association (MDA).

RG3039 is the first clinical-stage drug candidate to target the core genetic deficit in SMA in order to treat the biochemical deficits caused by decreased levels of the survival motor neuron (SMN) protein. This key protein is necessary for normal neuromuscular function but is insufficiently produced in SMA patients. RG3039 is an orally bioavailable small molecule inhibitor of an RNA processing enzyme called DcpS. RG3039 has been shown to increase production of the SMN protein in cells derived from patients. In addition, RG3039 has been shown to improve motor neuron pathology, mobility and lifespan in animal models of SMA.

Top-line results from this Phase 1 study of RG3039 are scheduled to be presented as part of a special neuroscience program at the 64th Annual Meeting of the American Academy of Neurology (AAN). The AAN meeting is being held April 21-28, 2012 at the New Orleans Ernest N. Morial Convention Center. James P. Van Meerbeke, Research Assistant from the lab of Charlotte J. Sumner, M.D., Associate Professor of Neurology and Neuroscience, Johns Hopkins University School of Medicine, will present the abstract titled “The Therapeutics Effects of RG3039 in Severe Spinal Muscular Atrophy – Mice and Normal Human Volunteers,” during “The Future of Neuroscience Conference: Neurologists and Neuroscientists Defining the Next Generation of CNS Therapies,” taking place on April 27.

In addition to the Phase 1 clinical trial outcomes, the AAN presentation highlights the results of earlier mouse model studies conducted with RG3039 at Johns Hopkins University and in the lab of Dr. Chien-Ping Ko at University of Southern California. In these preclinical studies, which provided proof of principle for conducting human clinical studies, administration of RG3039 resulted in a significant improvement in survival, increased maximum body weight and improved motor behavior in severe SMA mice. The effects were associated with increased SMN2 transcript levels and improved neuromuscular junction morphology and physiology. At therapeutic levels of RG3039 in mice, the target enzyme DcpS was inhibited greater than 90%. This appears to parallel outcomes from the Phase 1 human study, which achieved greater than 90% inhibition of DcpS in peripheral blood cells for 48 hours with a single dose of RG3039 and in absence of any toxicity.

In addition to the presentation at AAN, Dr. David Jacoby, Medical Director at Repligen Corporation, will present the RG3039 Phase 1 study outcomes during the 2012 International SMA Research Group Meeting. This FSMA organized meeting is being held in Minneapolis from June 21-23, 2012. Dr. Jacoby’s presentation titled, “A Phase I Study in Healthy Volunteers to Assess the Safety, Pharmacokinetics and Pharmacodynamics of the DcpS inhibitor RG3039,” is scheduled for Friday, June 22, 2012 at 3:40 p.m.